Hyaluronan is a long-chain polysaccharide comprising disaccharide repeats of D-glucuronic acid and N-acetyl-D-glucosamine, and it is also known as an oligosaccharide. Hyaluronan is produced from an extract of a body tissue such as the cock's crest, umbilical cord, skin, or synovial fluid, by fermentation using bacteria of the genus Streptococcus, or the like. Since it has no toxicological or immunological effects, hyaluronan is utilized in drugs or cosmetics. For example, treatment of arthritis using an intraarticular injection of hyaluronan is well known. In the following description, HA4 denotes a tetrasaccharide hyaluronan.
It has been reported that HA4 has effects of preserving organs and treating/suppressing hepatopathy and stomach ulcers (Patent Document 1). Furthermore, HA4 is also known to have actions of enhancing the expression of stress proteins and inhibiting cell death (Non-patent Document 1).
Osteoarthritis is a joint disease associated with chronic arthritis, in which degeneration of components of the joint leads to destruction of the cartilage and proliferative change of the bone and cartilage. Furthermore, arthritis (synovitis) occurs secondarily due to the above-mentioned change. At an early stage, pain occurs after overuse of a joint and is relieved with rest. When the disease progresses, pain occurs even during light exercise or at rest, and night pain is often noted. Strong joint bending or extending or exercise makes a rapping noise, and accumulation of a synovial fluid may also occur due to the arthritic swollen joint.
On top of the degeneration of joint components (change with aging), genetic factors, aging, obesity, joint instability, repeated subluxation and luxation, excessive loads on joints due to labor, playing sports, and the like, and so forth are associated with progression of the disease.
Early treatments include administration of anti-inflammatory or analgesic drugs and application of a poultice or a tape containing an analgesic to relieve the pain. Exercise for strengthening the quadriceps femoris is effective for treatment of the knees. Exercise for abduction (lying and raising a leg) is effective for treatment of the hip joints. The use of a cane is also effective for osteoarthritis in the knee or hip joints since it reduces the load on the joints. Intraarticular injection of a joint protecting drug is also effective. Intraarticular steroid injection therapy should be performed with care since it may accelerate joint destruction if abused. When pain or degeneration is severe, surgical operations such as osteotomy and replacement with an artificial joint are indicated for treatment of the knee or hip joint.    [Patent Document 1] WO2002/004471    [Non-patent Document 1] Xu H, Ito T, Tawada A, Maeda H, Yamanokuchi H, Isahara K, Yoshida K, Uchiyama Y, Asari A. Effect of hyaluronan oligosaccharides on the expression of heat shock protein 72. J Biol Chem. 2002 10; 277(19): 17308-14.